Effect of Ezetimibe Plus Simvastatin Versus Simvastatin Alone on Atherosclerosis in the Carotid Artery (ENHANCE)(P02578)

NCT00552097 | Completed Phase 3

• 1 other identifier: P02578
• Study Type: interventional
• Target: 720
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of the study is to determine whether ezetimibe plus simvastatin will be more effective than simvastatin alone in preventing progression of atherosclerosis of the inner layer of the carotid artery.

Conditions

Atherosclerosis; Hypercholesterolemia; Hyperlipoproteinemia Type II

Outcome Measures

Primary Outcomes (1)

• Change in ultrasound-determined average carotid artery intima-media thickness (IMT) on a per subject basis between baseline and endpoint.

  24 months

Secondary Outcomes (4)

• Proportion of subjects with a reduction in ultrasound-determined average carotid artery IMT between baseline and endpoint.

  24 months

• Change in ultrasound-determined maximum carotid artery IMT on a per subject basis between baseline and endpoint.

  24 months

• Proportion of subjects developing new carotid artery plaques between baseline and endpoint.

  24 months

• Change in ultrasound-determined average carotid artery plus average common femoral artery IMT on a per subject basis between baseline and endpoint.

  24 months

Study Arms (2)

EZ/Simva

EXPERIMENTAL

Drug: ezetimibe (plus simvastatin)

Placebo/Simva

PLACEBO COMPARATOR

Drug: placebo (plus simvastatin)

Interventions

ezetimibe (plus simvastatin) DRUG

oral tablets; ezetimibe 10 mg (plus simvastatin 80 mg) once daily for 24 months

Also known as: ZETIA, VYTORIN, SCH 58235, SCH 465981

EZ/Simva

placebo (plus simvastatin) DRUG

tablets; placebo to match ezetimibe 10 mg (plus simvastatin 80 mg) once daily for 24 months

Placebo/Simva

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Genotype-confirmed heterozygous familial hypercholesterolemia with written documentation of the genetic diagnosis at the time of screening and LDL-C \>=210 mg/dL (5.43 mmol/L), or clinical diagnosis of heterozygous familial hypercholesterolemia, defined as LDL-C \>=210 mg/dL (5.43 mmol/L) and at least one of the following:
• tendinous xanthoma
• child \<18 years of age with hypercholesterolemia (LDL-C \>159 mg/dL (4.11 mmol/L)
• has a sibling with hypercholesterolemia (LDL-C \>190 mg/dL \[4.91 mmol/L\]) and tendinous xanthoma
• LDL-C \>=210 mg/dL (5.43 mmol/L) 1 week before randomization
• plasma triglyceride level \<=400 mg/dL (4.52 mmol/L)

You may not qualify if:

• pregnancy or any other situation, condition, or illness that, in the opinion of the investigator, may interfere with optimal participation in the study
• presence of an apolipoprotein B gene mutation with confirmed absence of an LDL receptor mutation in either allele
• undergoing LDL-apheresis or plasma apheresis
• unsuitable plaque or artery morphology
• use of certain drugs, foods, or other agents known to alter cholesterol levels or to cause pharmacokinetic interactions with either ezetimibe or simvastatin

Sponsors & Collaborators

• Organon and Co: lead
• Merck Sharp & Dohme LLC: collaborator

Related Publications (2)

• Kastelein JJ, Sager PT, de Groot E, Veltri E. Comparison of ezetimibe plus simvastatin versus simvastatin monotherapy on atherosclerosis progression in familial hypercholesterolemia. Design and rationale of the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) trial. Am Heart J. 2005 Feb;149(2):234-9. doi: 10.1016/j.ahj.2004.06.024.

  PMID: 15846260 BACKGROUND

• Kastelein JJ, Akdim F, Stroes ES, Zwinderman AH, Bots ML, Stalenhoef AF, Visseren FL, Sijbrands EJ, Trip MD, Stein EA, Gaudet D, Duivenvoorden R, Veltri EP, Marais AD, de Groot E; ENHANCE Investigators. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med. 2008 Apr 3;358(14):1431-43. doi: 10.1056/NEJMoa0800742. Epub 2008 Mar 30.

  PMID: 18376000 DERIVED

MeSH Terms

Conditions

Atherosclerosis; Hypercholesterolemia; Hyperlipoproteinemia Type II

Interventions

Ezetimibe; Ezetimibe, Simvastatin Drug Combination

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Simvastatin; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2007
• First Posted: November 1, 2007
• Study Start: June 1, 2002
• Primary Completion: April 25, 2006
• Study Completion: April 25, 2006
• Last Updated: August 15, 2024

Record last verified: 2022-02